Sebastian-Patrick Sommer

Ischemia-reperfusion injury–induced pulmonary mitochondrial damage

BACKGROUND Mitochondrial dysfunction is a key factor in solid organ ischemia-reperfusion (IR) injury. Impaired mitochondrial integrity predisposes to cellular energy depletion, free radical generation, and cell death. This study analyzed mitochondrial damage induced by warm pulmonary IR. METHODS Anesthetized Wistar rats received mechanical ventilation. Pulmonary clamping was followed by reperfusion to generate IR injury. Rats were subjected to control, sham, and to 2 study group conditions: 30 minutes of ischemia without reperfusion (IR30/0), or ischemia followed by 60 minutes of reperfusion (IR30/60). Pulmonary edema was quantified by wet/dry-weight ratio. Polarography determined activities of respiratory chain complexes. Mitochondrial viability was detected by using Ca(2+)-induced swelling, and integrity by citrate synthase assay. Enzyme-linked immunosorbent assay determined cytochrome C content. Mitochondrial membrane potential (ΔΨm) stability was analyzed by flow cytometry using JC1, inflammation by myeloperoxidase (MPO) activity, and matrix-metalloproteinase-9 (MMP-9) activity by gel zymography, respectively. RESULTS In IR30/60 rats, tissue water content was elevated from 80.6 % (sham) to 86.9%. After ischemia, ΔΨm showed hyperpolarization and rapid decline after uncoupling compared with controls. IR, but not ischemia alone, impaired respiratory chain function complexes I, II and III (p < 0.05). Mitochondrial viability (p < 0.001) and integrity (p < 0.01) was impaired after ischemia and IR, followed by mitochondrial cytochrome C loss (p < 0.05). Increased activation of MPO (p < 0.01) and MMP-9 (p < 0.001) was induced by reperfusion after ischemia. CONCLUSIONS Ischemia-related ΔΨm hyper-polarization induces reperfusion-associated mitochondrial respiratory chain dysfunction in parallel with tissue inflammation and degradation. Controlling ΔΨm during ischemia might reduce IR injury.

Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats

This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum clamping followed by 60 min reperfusion time. Rats were subjected to controls, shams and two study groups (IR30/60, Gly-IR30/60) receiving 37.5 mg Gly i.v. or not before IR induction. The wet/dry-weight ratio, mitochondria viability (MV), membrane integrity (MI), respiratory chain complex (RCC) activities, mitochondrial membrane potential (ΔΨm) and cytochrome C (Cyt C) content were analysed. In IR30/60, RCC and MV were impaired; Cyt C loss and MI combined with matrix metalloproteinase-9 (MMP-9) activation and ΔΨm alteration were observed when compared with controls. In Gly-IR30/60, complex II function and mitochondrial viability were protected during IR, and MMP-9 activation combined with tissue-water content accumulation and ΔΨm alteration were ameliorated. Cyt C loss, mitochondrial membranes damage, tissue GSH oxidation or neutrophil sequestration was not extenuated in Gly-IR30/60. Gly ameliorates IR-associated mitochondrial dysfunction and decay of viability and normalizes ΔΨm but does not protect from Cyt C liberation and mitochondrial membrane damage. Our data suggest that the previously described effect of Gly preconditioning results at least partially from mitochondrial protection. A dose-finding study is necessary to improve results of Gly preconditioning.

Cardiac surgery and hematologic malignancies: a retrospective single-center analysis of 56 consecutive patients

OBJECTIVE Patients with a history of hematologic malignancies (HMs) are considered high-risk candidates for cardiac surgery. Increased perioperative rates of infections, thrombo-embolic complications, and bleeding disorders are reported. However, low patient numbers and lack of control groups limit all published studies. METHODS A total of 56 patients with a history of HM underwent cardiac surgery. As many as 29 patients suffered from non-Hodgkin lymphoma, five from Hodgkin disease, and 12 from myeloproliferative disorders, one from acute lymphatic leukemia, and nine from monoclonal gammopathy. Surgery consisted of coronary artery bypass grafting, valvular surgery or combination procedures. HM patients were matched to 142 controls. Matching criteria applied consisted of sex, age, main diagnosis, and co-morbidities. RESULTS In-hospital mortality was elevated in HM patients though not reaching significance (P = 0.7). HM patients demonstrated increased rates of vascular, pulmonary, infectious complications (P > 0.1), and transfusion requirements (P = 0.077). The long-term survival of HM patients was significantly impaired (P = 0.043). A history of irradiation or chemotherapy predisposed to postoperative respiratory insufficiency, acute renal failure, and an impaired long-term survival (P > 0.065). CONCLUSIONS Cardiac surgery in patients with a history of a malignant hematologic disorder might achieve acceptable results. However, a higher complication and mortality rate have to be anticipated. Patients with hematologic disorders and a history of either irradiation or chemotherapy appear to be at an increased risk to develop postoperative end-organ failure.

Cardiac surgery antibiotic prophylaxis and calculated empiric antibiotic therapy

Background Ongoing debate exists concerning the optimal choice and duration of antibiotic prophylaxis as well as the reasonable calculated empiric antibiotic therapy for hospital-acquired infections in critically ill cardiac surgery patients. Methods A nationwide questionnaire was distributed to all German heart surgery centers concerning antibiotic prophylaxis and the calculated empiric antibiotic therapy. Results The response to the questionnaire was 87.3%. All clinics that responded use antibiotic prophylaxis, 79% perform it not longer than 24 h (single-shot: 23%; 2 doses: 29%; 3 doses: 27%; 4 doses: 13%; and >5 doses: 8%). Cephalosporin was used in 89% of clinics (46% second-generation, 43% first-generation cephalosporin). If sepsis is suspected, the following diagnostics are performed routinely: wound inspection 100%; white blood cell count 100%; radiography 99%; C-reactive protein 97%; microbiological testing of urine 91%, blood 81%, and bronchial secretion 81%; procalcitonin 74%; and echocardiography 75%. The calculated empiric antibiotic therapy (depending on the suspected focus) consists of a multidrug combination with broad-spectrum agents. Conclusion This survey shows that existing national guidelines and recommendations concerning perioperative antibiotic prophylaxis and calculated empiric antibiotic therapy are well applied in almost all German heart centers.

Impact of levosimendan and ischaemia–reperfusion injury on myocardial subsarcolemmal mitochondrial respiratory chain, mitochondrial membrane potential, Ca2+ cycling and ATP synthesis

OBJECTIVES Levosimendan (LS) is increasingly used in case of myocardial failure after cardiac surgery. The impact of LS on myocardial mitochondrial functions, such as respiratory chain function (RCF), mitochondrial membrane potential (ΔΨm), Ca(2+) handling, mitochondrial permeability transition pore (mPTP) opening and ATP during ongoing ischaemia/reperfusion (IR) injury, is not well understood. Depending on LS, I/R injury or the combination of both, we analysed myocardial functions in a retrograde Langendorff-model followed by the analysis of subsarcolemmal mitochondrial (SSM) functions. METHODS Rat hearts were divided into four study groups; two were subjected to 30 min of perfusion without (control) or with the application of 1.4 µmol/20 min LS (Levo). Experiments were repeated with hearts being subjected to 40 min of normothermic stop-flow ischaemia and 30 min of reperfusion without (IR) or with LS application (Levo-IR). Systolic left ventricular pressure (LVPsys), left ventricular contractility (LVdp/dtmax) and coronary flow were determined. SSM were analysed regarding RCF, ΔΨm, ATP, and Ca(2+) retention capacity (CRC), Ca(2+)-induced swelling and Ca(2+) fluxes after (re)perfusion. RESULTS I/R injury suppressed LVdp/dtmax (1381 ± 927 vs 2464 ± 913 mmHg/s; P = 0.01 at 30 min (re-)perfusion time). IR revealed complex I-V state3 (19.1 ± 7.4 vs 27.6 ± 11.0 nmolO2/min; P < 0.044) and II-V state3 (20.6 ± 6.8 vs 37.3 ± 9.10 molO2/min; P < 0.0001) suppression and Levo limited I-V (14.8 ± 11.1 vs 27.6 ± 11.0 nmolO2/min; P < 0.001) and II-V (24.1 ± 6.4 vs 37.3 ± 9.10 molO2/min; P < 0.0001) function. After energizing, ΔΨm hypopolarization was observed in Levo (0.76 ± 0.04 vs 0.84 ± 0.04; P = 0.02), IR (0.75 ± 0.06 vs 0.84 ± 0.04; P = 0.007) and Levo-IR (0.75 ± 0.06 vs 0.06 ± 0.04; P = 0.01). IR (AUC: 626 vs 292; P = 0.023) and Levo-IR (AUC: 683 vs 292, P = 0.003) increased Ca(2+)-induced mPTP-opening susceptibility. CRC declined in IR (6.4 ± 2.1 vs 10.5 ± 2.6; P = 0.04) or Levo (6.5 ± 2.0 vs 10.5 ± 2.6; P = 0.023). Ca(2+) uptake was delayed in IR and Levo-IR without LS impact (P < 0.0001). Ca(2+) liberation was increased in Levo-IR. ATP synthesis was reduced in Levo (0.49 ± 0.14 vs 0.74 ± 0.14; P = 0.002) and Levo-I/R (0.34 ± 0.18 vs 0.74 ± 0.14; P < 0.002). CONCLUSION LS limited RCF at complex IV and V with ΔΨm hypopolarization suggesting a specific [Formula: see text]-dependent pathway. Ca(2+) redistribution from SSM by LS during I/R injury possibly prevents from Ca(2+) overload due to mPTP flickering. LS-induced mPTP flickering did not promote permanent Ca(2+)-induced mPTP opening. LS-dependent inhibition of ATP generation presumably resulted from complex IV and V limitations and lowered ΔΨm. However, a resulting impact of limited ATP synthesis on myocardial recovery remains arguable.

Secondary sclerosing cholangitis in cardiac surgical patients: A complication with a dismal prognosis

Objectives: Secondary sclerosing cholangitis in critically ill patients is a rapidly progressing disease leading to biliary fibrosis and cirrhosis. We describe the course of sclerosing cholangitis in critically ill patients after cardiac surgery and compare this with matched patients. Methods: A retrospective search for “secondary sclerosing cholangitis” and “liver and/or hepatic failure” in all adult patients (aged 18‐93 years) who underwent cardiac surgery from April 2007 to March 2016 identified 192 of 8625 patients. Of those, 12 were diagnosed with sclerosing cholangitis in critically ill patients (incidence, 0.14%). A 3:1 matching was performed. Laboratory values, pharmacologic requirements, ventilation times, mechanical circulatory support, and endoscopic retrograde cholangiopancreatography studies were extracted from the hospital database. Results: A total of 9 men and 3 women were affected (age 71 years; range, 59.8‐75.5 years). Critically ill patients with sclerosing cholangitis required vasoconstrictors and inotropes longer than control patients (norepinephrine 356.5 hours [264.5‐621] vs 68 hours [15‐132.5], P = .003; enoximone 177 hours [124.3‐249.5] vs 48.5 hours [12‐81 hours], P < .001, respectively). Critically ill patients with sclerosing cholangitis had longer intubation time (628.5 hours [377.3‐883] vs 25 hours [9.8‐117.5]; P < .001) and more surgical revisions (3 [2.5‐6] vs 1 [0‐2], P = .003) than the matching group. Bilirubin (23.3 mg/dL [14.4‐32.9] vs 1 mg/dL [0.6‐2.7]; P < .001), gamma‐glutamyltransferase (1082.3 U/L [259.5‐2265.7] vs 53.8 U/L [35.1‐146]; P < .001), and alkaline phosphatase (751.5 U/L [372‐1722.3] vs 80.5 U/L [53.3‐122]; P < .001) were higher in critically ill patients with sclerosing cholangitis. One critically ill patient with sclerosing cholangitis underwent successful liver transplantation. A total of 11 patients sclerosing cholangitis died (92%) versus 12 patients (33%, P < .001) in the control group. Conclusions: Sclerosing cholangitis in critically ill patients is a fatal complication in patients undergoing cardiac surgery who have a complicated postoperative course with prolonged vasoconstrictor, inotropic, and respiratory therapy, or who require frequent surgical revisions. Liver transplantation remains the only curative option but is often precluded by the age and critical state of patients undergoing cardiac surgery.

Initial topical cooling followed by backtable Celsior flush perfusion provides excellent early graft function in porcine single lung transplantation after 24 hours of cold ischemia

BACKGROUND Topical in situ cooling of the donor lungs is a prerequisite for procurement of non-heart-beating donor lungs and may be of interest for living related lung donation. METHODS Twenty-four single lung transplants were performed in 4 groups of Landrace pigs (6 per group). Control LPD, control Celsior and topical cooling in situ, followed by LPD (exLPD) or Celsior (exCel) ex situ flush, were employed. All lungs were perfused antegrade with 1 liter of solution at 4°C. Lungs were stored immersed in preservation solution for 24 hours at 4°C. After transplantation of the left lung, the right recipient bronchus and pulmonary artery were clamped. RESULTS Four of 6 animals each in the LPD and Celsior groups and all 6 animals in both the exLPD and the exCel groups survived the 7-hour reperfusion. The mean oxygenation index was favorably preserved in the exCel group at 7 hours after reperfusion (417 ± 81) over all other groups (LPD 341 ± 133, Celsior 387 ± 86, exLPD 327 ± 76; p < 0.0001). Pulmonary vascular resistance showed significantly lower values in the Celsior and exCel groups (LPD 1,310 ± 620, Celsior 584 ± 194, exLPD 1,035 ± 361, exCel 650 ± 116 dyn/s/cm(5) at 7 hours after reperfusion; p < 0.0001). Consistently, the wet-to-dry lung weight ratio also indicated beneficial graft protection in the exCel group (LPD 8.1 ± 0.8, Celsior 8.4 ± 0.8, exLPD 7.5 ± 1.0, exCel 3.1 ± 0.9; p < 0.0001). CONCLUSION Initial topical cooling followed by backtable perfusion is a sufficient technique for pulmonary graft preservation providing excellent post-transplant function. Celsior subsequent to in-situ topical cooling revealed the most beneficial results in this setting. This combined technique could advance non-heart-beating, living related lung lobe donation and, potentially, regular heart-beating lung donation.

Injury to the thoracic aorta

SummaryBACKGROUND: This article reviews the mechanisms of thoracic aortic injury and therapeutic options for its repair. METHODS: We retrospectively analyze our data on surgery of the thoracic aorta for blunt trauma in 25 patients during the last two decades. RESULTS: Blunt aortic trauma is a rare but life-threatening incident, mainly resulting from deceleration forces in vehicle accidents and falls from a height. Dissection and rupture of the descending aorta distal to the left subclavian artery is the most frequently seen pathological correlate. Iatrogenic injuries resulting from cardiovascular surgery and endovascular interventions may also cause aortic trauma. Results of surgery in acute cases are less good than in a stable subacute or chronic phase (mortality, 20% vs. 0%). CONCLUSIONS: Traumatic injury to the thoracic aorta is a potentially lethal problem. When acute traumatic dissection or rupture of the thoracic aorta is diagnosed, surgical aortic repair must be performed immediately. In an unstable patient or if a contraindication for surgery exists, an endovascular stent graft prosthesis is a rational alternative. For acute aortic replacement, use of extracorporeal circulation is essential for organ protection and for a satisfactory surgical outcome.ZusammenfassungGRUNDLAGEN: Dieser Beitrag stellt Ursachen und Mechanismen thorakaler Aortenverletzungen und deren mögliche Behandlungsstrategien dar. METHODIK: Unsere Daten bezüglich stumpfer thorakaler Aortenverletzungen bei 25 Patienten der letzten zwei Dekaden werden retrospektiv analysiert. ERGEBNISSE: Ein stumpfes Trauma der thorakalen Hauptschlagader ist selten, jedoch lebensbedrohlich und resultiert zumeist aus Autounfällen oder Fall aus großer Höhe. Das am häufigsten gesehene pathologische Korrelat ist eine Dissektion und Ruptur der deszendierenden Aorta, distal des Abgangs der linken Armschlagader. Weitere Ursachen für Traumen der Aorta sind iatrogen, etwa nach kardiovaskulären Operationen oder interventionellen endovaskulären Eingriffen. Die Ergebnisse der Akutoperation nach stumpfem Aortentrauma sind weniger günstig als in der stabilen subakuten oder chronischen Phase (Mortalität, 20 % vs. 0 %). SCHLUSSFOLGERUNGEN: Die traumatische Verletzung der thorakalen Aorta stellt ein potentiell letales Problem dar. Wird eine akute traumatische Dissektion oder eine Ruptur der thorakalen Aorta diagnostiziert, muss unverzüglich die chirurgische Sanierung erfolgen. Bei instabilen Patienten oder wenn schwerwiegende Kontraindikationen bestehen, ist die Verwendung endovaskulärer Stent Grafts eine rationale Alternative. Für den akuten Aortenersatz ist die Anwendung der extrakorporalen Zirkulation zur Organprotektion und für ein zufriedenstellendes chirurgisches Ergebnis unverzichtbar.

A new technique to implant a transcatheter inflatable, fully repositionable prosthesis in aortic stenosis with severe asymmetric calcification†

OBJECTIVES In contrast to stented transcatheter aortic valves, the Direct Flow Medical (DFM) valve is a stentless bovine aortic bioprosthesis mounted in a non-metallic inflatable frame. Hence, severe asymmetric annular calcification may result in residually elevated transaortic pressure gradients after DFM implantation. We present a novel intraprocedural dilatation (IDIL) technique for successful implantation of the DFM valve in the presence of complex annular calcification. METHODS Between January 2014 and May 2015, 55 patients underwent DFM valve-based transcatheter aortic valve implantation at our institution. Of these, 5 patients required an IDIL technique due to a residual intraoperative transaortic pressure mean gradient above 15 mmHg. The mean patient age was 73 ± 8.2 years; the mean logistic EuroSCORE was 24.5 ± 8.2% and the mean Society of Thoracic Surgeons score was 6.3 ± 4.3%. RESULTS The IDIL technique immediately attenuated transvalvular mean pressure gradients from 20 ± 2 mmHg to 6 ± 1 mmHg. The results remained stable during the 30-day observation period at 10 ± 3 mmHg. Minimal paravalvular aortic regurgitation (trace) was detected in 2 patients. No in-hospital deaths were observed. CONCLUSIONS The IDIL technique facilitates safe DFM valve implantation in patients with complex asymmetric annular calcification without adverse side effects on valve structure or performance in short-term follow-up.

Cardiac Surgery is Safe in Female Patients with a History of Breast Cancer

PURPOSE In cardiac surgery candidates, a concomitant history of breast cancer suggests adverse outcomes. The possibility of internal mammary artery (IMA) utilization and its patency rate is frequently discussed. Secondary, blood loss and wound related infections might be important issues. However, publications focusing on these issues are limited. METHODS We analyzed 32 patients with previously treated breast cancer undergoing cardiac bypass (CABG) and combined CABG surgery matched to 99 control subjects in a retrospective cohort study. Patients were analyzed regarding IMA utilization, blood loss and substitution and frequent perioperative complications as well as long-term mortality. RESULTS No significant differences between groups were observed regarding duration of surgery, IMA-utilization, incidence of infections and postoperative complications or mortality. A pronounced decline of hemoglobin/hematocrit was evident within the first 6 postoperative hours (3.3 ± 1.8 vs. 2.5 ± 1.8 mg/dl; p = 0.03) in breast cancer patients not related to an increased drainage loss but associated with an increase of international normalized ratio (INR) (0.39 ± 0.16 vs. 0.29 ± 0.24; p <0.01). CONCLUSION In breast cancer patients, CABG and combined CABG procedures can safely be performed with comparable short- and long-term results.